1. Field of the Invention
The present invention relates to the isolation of atraric acid from biological material, to atraric acid derivatives, to the chemical synthesis thereof, as well as to the use of atraric acid and of the derivatives thereof for the treatment or the production of a medicament for treating benign prostate hyperplasia and/or prostate carcinoma, particularly therapy-resistant prostate carcinoma, as well as spinobulbar muscular atrophy. The present invention furthermore relates to the use of atraric acid and its derivatives as the lead substance in the development of new active substances for the treatment or the production of a medicament used for treating benign prostatic hyperplasia and/or prostate carcinoma, particularly therapy-resistant prostate carcinoma, as well as spinobulbar muscular atrophy.
2. Description of the Prior Art
Benign prostatic hyperplasia (BPH) is a benign enlargement of the glandular epithelium, of the connective tissue and of the smooth muscles in the transitional zone of the prostate. BPH afflicts 50% of men over 60 years of age, in men over 75 years of age the percentage is even 75%. Thus, BPH is responsible for the most frequent form of bladder dysfunction in men.
The symptoms of BPH comprise obstructive and irritative complaints. The obstructive symptoms include diminished urinary stream, prolonged micturation time, dribbling and residual urine, while the irritative symptoms are manifested in increased micturation frequency, painful micturation, and urge incontinence. Regarding the etiology of BPH, there are various hypotheses currently being discussed.
Prostate carcinoma is the most common cancer affecting men in the Western countries and represents the second most common cause of cancer death after lung cancer. Although, in its etiology, the prostate carcinoma is not directly connected to BPH, patients suffering from a severe form of BPH show gene anomalies that are very similar to those of prostate cancer patients. While BPH affects above all the transitional zone of the prostate, a carcinoma occurs preferably in the peripheral zone.
The reasons for the development of a prostate carcinoma are various gene defects, which may be due to a predisposition in the family. Thus, various mutations of the androgen receptor occur in the persons suffering from prostate carcinoma. Reduced activity of the 5 α-reductase type II, however, reduces the risk of developing a carcinoma. Furthermore, different tumour suppressor genes, such as Rb gene on chromosome 13 q, can be affected by mutations and can thus become inactivated. On the other hand, a hyperfunction of oncogenes contributes to tumour formation. In addition, a significant role is played by methylations of important growth-regulating and detoxifying genes, the genes thereby becoming unable to function and clearing the way for cancer. According to the most recent state of science, a big contribution is made by inflammation processes from which emanate preneoplastic or neoplastic lesions.
The initial therapy for treating prostate carcinoma usually consists in removing the prostate by radical prostatectomy, or in irradiation to remove the degenerated cells. An advanced, metastasising prostate carcinoma can be treated by a palliative hormone therapy. The total androgen blockade, which is applied nowadays, includes the combination of operative and chemical castration. The purely antiandrogenic agents bicalutamide (CASODEX®), flutamide (FUGEREL®) and nilutamide (ANANDRON®) act selectively on the androgen receptors of the target organs while cyproterone acetate (ANDROCUR®) also occupies progesterone receptors and glucocorticoid receptors. However, hormone therapy cannot heal advanced prostate cancer. The treatment initially causes an antiandrogen-dependent inhibition of tumour growth. However, after two years, on average, resistance to the therapy occurs. First, a hyperexpression of various coactivators enables the activation of the androgen receptor through non-androgenic steroids. Later on, even antiandrogens, such as the active flutamide metabolite, 2-hydroxyflutamide, are able to activate the androgen receptor, and the tumour becomes independent of androgens.